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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 14  |  Issue : 2  |  Page : 188-193

Transrectal ultrasonography and biopsy of the prostate


1 Department of Urology, J. N. Medical College, KLE Academy of Higher Education and Research (Deemed-To-Be- University); KLES Kidney Foundation, KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi, Karnataka, India
2 Department of Urology, J. N. Medical College, KLE Academy of Higher Education and Research (Deemed-To-Be-University), Belagavi, Karnataka, India
3 Department of Urology, Urinary Biomarker Research Centre, KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi, Karnataka, India

Date of Submission01-Feb-2019
Date of Acceptance12-May-2020
Date of Web Publication31-May-2021

Correspondence Address:
Dr. R B Nerli
Department of Urology, KLE Academy of Higher Education and Research (Deemed.to.Be. University), JNMC Campus, Belagavi - 590 010, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kleuhsj.kleuhsj_5_19

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  Abstract 


When compared to other solid organ malignancies, the diagnosis of prostate cancer is not reliant on imaging findings alone. Men found to have abnormal digital rectal examination findings, raised serum prostate-specific antigen levels, or both are subjected to prostate biopsy to arrive at a diagnosis. Since its introduction in the 1970s, Transrectal ultrasonography (TRUS) plays a vital role in the diagnostic pathway to guide prostatic biopsy. However, many men are subjected to unnecessary biopsies, leading to a diagnosis of clinically-indolent cancer or occasionally missing a focus of clinically significant disease. Currently, TRUS-guided prostate biopsy performed under local anesthesia is in widespread use for the diagnosis of prostate cancer. The peripheral zone of the prostate showing a hypoechoic lesion is the most common finding consistent with prostate cancer. In this review, we aim to highlight the ultrasonographic anatomy of prostate, the technique, and associated complications along with a brief note on the recent advances in imaging technology for the diagnosis of prostate cancer.

Keywords: Early detection of cancer, prostate biopsy, prostate cancer, transrectal ultrasonography


How to cite this article:
Nerli R B, Sharma M, Ghagane SC. Transrectal ultrasonography and biopsy of the prostate. Indian J Health Sci Biomed Res 2021;14:188-93

How to cite this URL:
Nerli R B, Sharma M, Ghagane SC. Transrectal ultrasonography and biopsy of the prostate. Indian J Health Sci Biomed Res [serial online] 2021 [cited 2021 Jun 17];14:188-93. Available from: https://www.ijournalhs.org/text.asp?2021/14/2/188/317391




  Introduction Top


Prostate cancer is the most prevalent malignancy affecting older men in most of the developed world and is accountable for around 13% of all cancer deaths in men.[1] In India, too, it is among the top 10 cancers affecting males. In the United Kingdom, the lifetime risk of being diagnosed with prostate cancer is one in nine.[1] Postmortem data have revealed that roughly half of all men in their fifth decade have prostate cancer, which escalates to about 80% by the eighth decade of life. However, only 1 in 26 men eventually succumbs to the disease, supporting the fact that men are more probable to die with prostate cancer than from it.[2],[3]

With the introduction of widespread prostate-specific antigen (PSA) testing in 1987, there was an exponential rise in the incidence of prostate cancer in the United States.[4] The absence of randomized trials documenting that early detection and aggressive treatment of prostate cancer can reduce mortality has made PSA screening controversial. The advent of PSA screening has led to the lifetime risk of a diagnosis of prostate cancer to about 16% today, whereas the lifetime risk of death from prostate cancer is about 3.4%.[5] It is evident that most prostate cancers that are diagnosed today are not destined to be fatal. This is probably due to the relatively slow doubling time of early prostate cancer, commonly 3 years or more,[6] and to the fact that the diagnosis of cancer is frequently made in older men. They are more likely to die from cardiovascular diseases.

Early detection of prostate cancer not only reduces mortality but also helps in decreasing the morbidity due to hematuria, bladder outlet obstruction, and the development of painful bony metastases. Moreover, the finding of normal results on PSA testing may provide reassurance to men who are apprehensive about prostate cancer. However, the possibility of a false negative result must be acknowledged. PSA testing has its potential drawbacks. Aggressive management in the presence of an abnormal test result and a subsequent diagnosis of cancer. It also includes the anxiety associated with a false-positive result and the liability of dealing with cancers that otherwise might never have become apparent.

At present, the sensitivity and specificity of the PSA test are low. The PSA threshold at which a prostate biopsy is to be performed also remains unclear. Histopathological results of the prostatic biopsy remain the gold standard in the diagnosis of cancer of the prostate. However, biopsies are generally indicated only when the results of a PSA test or digital rectal examination raise suspicion. This often leads to workup bias with respect to defining the sensitivity and specificity of the PSA test and an overestimation of the sensitivity of the test in particular. The standard of care for men with suspicious findings on PSA tests and/or digital rectal examination is a transrectal ultrasonography (TRUS) - guided biopsy. Men with suspicious digital rectal examination findings and a PSA level of 4.0 ng per ml or less have a probability of cancer of at least 10%,[7],[8] and biopsy is usually recommended.


  Transrectal Ultrasonography Top


Transrectal ultrasonography (TRUS) has become a commonly used imaging modality in the practice of urology. Today, TRUS has been utilized in several image-guided prostate cancer interventions. These include initial prostate biopsy, follow-up biopsy for active surveillance, planning brachytherapy, cryotherapy, and high-intensity focused US.[9] Real-time tumor tracking of the prostate during radiation therapy is done by placement of Fiducial and radiofrequency markers under TRUS guidance.[10],[11] Rectal toxicity during prostate radiation therapy is decreased by TRUS-guided injection of polyethylene glycol hydrogel into anterior perirectal fat.[12] TRUS is also used in the evaluation of treatment options for Benign Prostatic Hyperplasia (BPH) and in some cases of male infertility.[9]

Watanabe et al.[13] were the first to describe the TRUS of the prostate. The practice of digitally guided prostatic biopsy gradually evolved into TRUS-guided prostate biopsies. Hodge et al.[14] introduced the TRUS-guided systematic sextant (six core), biopsy protocol. The use of serum PSA as a screening tool has increased the number of men undergoing prostate biopsy. This led to further improvement in biopsy techniques and also an increase in recommended biopsy cores to 12.

Anatomy of the prostate

The prostate lies anterior to the rectum, between the bladder neck and the urogenital diaphragm, an ideal position to be imaged through TRUS. The prostate gland is described based on a zonal architecture, as described by McNeal.[9] The prostate is divided into an anterior fibromuscular stroma, which is lacking glandular tissue, Transitional zone (TZ); central zone (CZ); periurethral zone; and peripheral zone (PZ). These zones, however, cannot be made out as distinct entities on the US examination. The peripheral zone is more echogenic when compared to the CZ and the Transitional Zone (TZ), which are echo poor. In a healthy adult, the CZ is difficult to distinguish from the TZ. In young adults, the PZ constitutes 75% of the gland volume, the CZ 20%, and the TZ 5%, but these ratios keep on changing with age and the onset of benign prostatic hyperplasia (BPH).

BPH commonly starts in the TZ and progressively occupies most of the gland, stretching and thinning the PZ. The ejaculatory ducts are visualized within the central gland, as echogenic tramlines on longitudinal scans. Ejaculatory ducts can be traced posteriorly to the ampulla of the vas. The vas deferens can be seen originating from the ampulla of vas between the seminal vesicles (SV). The bladder neck and external urethral sphincter (distal to the prostatic apex) can be seen as somewhat echo poor structures. This is due to anisotropy from the orientation of smooth muscle fibres relative to that of the prostate.[1] The prostate is devoid of a true capsule, but the prostate–fat interface forms a clear boundary around, and this has been termed the prostatic capsule. The capsule normally appears smooth and regular.

The neurovascular bundles are identified posterolateral to the prostate in the fat-filled echogenic triangular-shaped space between the SV and the prostate. The levator ani muscles appear as linear structures lateral to the prostatic bed. The prostatic volume is calculated using an ellipsoid formula by measuring the maximum anteroposterior, craniocaudal, and transverse distances and multiplying the product of these by π/6.

Gray-scale transrectal ultrasonography

Gray-scale TRUS is now the most commonly performed imaging for the prostate and is most commonly employed for the detection of prostate cancer. Today, endorectal probes are available in both side-and end-fire models and transmit frequencies ranging from 6 to 10 MHz [Figure 1]a and [Figure 1]b. Most modern US machines have enhanced self-programming for TRUS and biopsy. Some newer biplanar probes provide concurrent sagittal and transverse imaging modes. Probes provide a scanning angle approaching 180° to allow simultaneous visualization of the entire gland in both the transverse and sagittal planes.
Figure 1: (a) HITACHI Avius (Hi vision) Ultrasonography machine. (b) 7 MHz Transrectal probe CC531T/CC531 L

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Prostate cancer imaging on transrectal ultrasonography

Previously, hypoechoic lesions on TRUS examination were considered pathognomonic for prostate cancer. It is important to note all the hypoechoic lesions within the peripheral zone (PZ) and target them during prostate biopsy [Figure 2]. The absence of a distinct hypoechoic focus should not preclude from proceeding with biopsy, as 39% of all cancers are isoechoic, and up to 1% of tumors may be hyperechoic on conventional gray-scale TRUS.[9],[15] Studies have shown that biopsy samples taken from a prostate lesion identified by TRUS are almost twice more likely to show cancer than when no lesion is visible.[16] Toi et al. felt that the search for and targeting hypoechoic lesions on TRUS is crucial for the diagnosis of prostate cancer.[16]
Figure 2: (a) Color Doppler imaging showing hypervascularity around the peripheral hypoechoic lesion in the left lobe. (b) Rt. Lobe of prostate showing hypoechoic lesion, which revealed malignancy (Adenocarcinoma Gleason's score 4 + 4 = 8)

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  Prostate Biopsy: Techniques Top


Current indications for prostatic biopsy include elevated total PSA, free PSA <20%, PSA velocity >0.75 ng/ml per year, abnormal digital examination and prior negative biopsies, but persistent high suspicion for prostate cancer.[1] Absence of rectum, ilio-anal pouch, inflammatory bowel disease (especially Crohn's disease), and severe bleeding diatheses are absolute contraindications to TRUS biopsy. Patients on anticoagulation treatment should have their international normalized ratio corrected to <1.3. Relative contraindications to biopsy include acute prostatitis, perianal inflammation, fissure-in-ano, and severe hemorrhoids.[1]

The examination and biopsy can be done with the patient positioned in the left lateral decubitus or lithotomy position. The endorectal probe with the biopsy guide is inserted into the rectum after adequate lubrication and local anaesthetic administered around the prostate.

Preparation of patients for biopsy

Patients should be explained regarding the procedure, the risks and benefits of the procedure, and written informed consent must be obtained. If the patients are on low-dose aspirin, then they need not be discontinued. Anticoagulant therapy (warfarin, clopidogrel, etc.) should be stopped 7–10 days before prostate biopsy. If patients are on rivaroxaban, then stopping it may increase the risk of stroke, therefore bridging with some other anticoagulant such as heparin is recommended. The patient need not empty the bladder as a small amount of urine helps facilitate the examination by demonstrating the prostate-vesical junction.

Cleansing enema

Patients are advised to self-administer a cleansing enema at home before the biopsy. Enema reduces the amount of feces in the rectum, thus producing a superior acoustic window for prostate imaging. Whether the enema reduces the incidence of infections is a debatable issue.

Anesthesia

The use of local anesthetic for TRUS-guided biopsy is now standard practice.[17] A long lumbar puncture needle (7 inches, 22G) is used to administer 10 ml of 1% lidocaine.[18] The anesthetic agent is administered around the neurovascular bundle between the base of the gland and the SV, adjacent to the apex or into Denonvilliers' fascia. Injection of the drug directly into the gland is of no added benefit. Potential complications include pain caused by needle puncture, systematic lidocaine toxicity, temporary urinary incontinence (because of anesthesia of the external urethral sphincter), artefact formation on the TRUS image (from air introduced during injection), periprostatic infection and erectile dysfunction.[19]

Antibiotic prophylaxis

The potential for infection with Escherichia coli, anaerobes and Gram-positive organisms being high, antibiotic prophylaxis is the standard of care for all patients undergoing TRUS guided biopsy.[20] The incidence of infection following biopsy without antibiotic prophylaxis is quoted to be around 1%–6%, and resulting in septicaemia requiring hospitalization in 0%–4%.[21] Quinolones (predominantly ciprofloxacin) are the most commonly used prophylactic antibiotics.[22] EUA guidelines have recommended the use of a minimum of one oral antibiotic, such as a quinolone,[23] and is best given a few hours before the biopsy on the day of the procedure and may be continued for 3–5 days afterward.[24] Additional prophylaxis may be required in patients at risk of endocarditis. Recently, a rise in antibiotic-resistant organisms has been reported in patients after TRUS biopsy,[25] making it necessary to monitor local patterns of antibiotic resistance.

Biopsy number and technique

An initial digital rectal examination should be performed before performing TRUS and biopsy to evaluate for any prostate nodularity or anal pathologic processes. The prostate volume is determined, and the prostate is imaged in both the transverse and sagittal planes. The prostate is examined starting at the base of the gland and extending gradually to the apex. Most ultrasonography units are set for optimal prostate viewing, and the TRUS gray-scale examination of the prostate is conducted, noting the location and characteristics of any lesions (i.e. hypoechoic, hyperechoic, calcifications, contour abnormalities, cystic structures).

Routinely a spring-driven 18G needle core biopsy device or biopsy gun is used for biopsy. It is passed through the needle guide attached to the US probe. The ultrasonography units provide a good visualization of the biopsy needle path in the sagittal plane. Images are typically superimposed with a ruled puncture path that corresponds to the needle guide of the TRUS unit. The biopsy gun usually advances the needle 0.5 cm beyond the area to be sampled. Therefore, when sampling the PZ, the needle tip must be placed 0.5 cm posterior to the prostate capsule before firing.

The biopsy sample is placed in 10% formalin. The sample bottle is properly labeled regarding the site of the specimen. However, an AUA white paper did not provide compelling evidence that individual site-specific labeling of cores benefited clinical decision making regarding the management of prostate cancer.[26] The article recommended that no more than two cores were to be packaged in each jar to avoid the reduction of the cancer detection rate through inadequate tissue sampling. Hodge et al.,[14] who originally suggested a sextant biopsy scheme (one core from the base, mid, and apex bilaterally) opined that it significantly improved cancer detection rate over digitally directed biopsy of palpable nodules and US-guided biopsy of specific hypoechoic lesions.[14] Studies of radical prostatectomy specimens demonstrated that the vast majority of adenocarcinomas arise in the posterolateral PZ, thus explaining some of the false-negative results of standard sextant biopsy.[27]

As of today, six cores are considered inadequate for routine prostate biopsy for cancer detection. At present, the extended 12-core systematic biopsy that incorporates apical and far-lateral cores in the template distribution is commonly followed as it allows maximal cancer detection and avoids the need for a repeat biopsy and at the same time minimizes the detection of insignificant prostate cancers. This approach has been endorsed in an AUA white paper.[26],[28] Increasing the cores from 6 to 12 has led to a significant increase in cancer detection rate. However, increasing the number of cores to 18 or 21 (often termed saturation biopsy) as an initial biopsy strategy has not resulted in a similar increase. At present, a saturation biopsy is more likely to be indicated in the setting of a prior negative biopsy.

The TZ and SV are routinely not sampled because these regions have been shown to have consistently low yields for cancer detection at initial biopsy.[29] However, biopsies directed toward TZ and anterior zone may occasionally prove necessary to diagnose prostate cancer in those patients with persistently elevated PSA levels and prior negative biopsies.[30] Today, magnetic resonance imaging is often used to detect and guide biopsies of these anterior tumors that may escape standard TRUS prostate biopsy.[31] SV biopsy is not routinely performed unless there is a palpable abnormality, or when the PSA value is >30 or if brachytherapy is being considered.[32]

Complications

TRUS-guided prostatic biopsy is relatively safe, and the overall complication rate remains low. Pooled data have shown that the risks of infection and rectal bleeding are 0%–4% and 1.3%–5.8%, respectively.[1],[21],[25] Complications include hematospermia, bleeding per urethra, fever, urosepsis, rectal bleeding, urinary retention, prostatitis, and epididymitis.[1] Urinary retention and epididymitis are associated with an increase in the number of biopsy cores. Urinary retention can occur due to prostatic edema and may occur in the absence of haematuria.

The occurrence of hemorrhage increases with the number of biopsy cores. Severe hemorrhage leading to hospitalization is very rare and most likely occurs due to rectal artery or vein injury. It can also present hours after the biopsy. Hospitalization and transfusion may often be necessary in such cases, and urgent proctoscopy may be necessary to cauterize bleeding points from the suspected arterial bleeder. Direct compressing the rectal mucosa with the TRUS probe or a Foley catheter balloon may help as a temporizing measure until definitive treatment is given.


  Advanced and Investigational Techniques for Prostate Biopsy Top


Color and power Doppler transrectal ultrasonography

Color Doppler imaging is centered on the frequency shift and depicts the velocity of blood flow in a directionally dependent manner.[9] Color assignment is based on the direction of blood flow related to the orientation of the transducer receiving the signal; flow toward the transducer is depicted in shades of red and flow away in shades of blue; the color is not specific for arterial or venous flow. The advantages of power Doppler imaging are its ability to detect slower flow and less reliance on the Doppler angle, making it more suitable for the detection of prostate cancer neovascularity. The normal prostate gland has little blood flow, but what is present is usually symmetrical. Strong Doppler signals are usually seen at the site of neurovascular bundles and peri-capsular and peri-urethral arteries.

Originally, it was thought that the use of colour/power Doppler techniques increased the chance of detection of cancer, but had a poor specificity. Turgut et al.[33] found that using power Doppler could be useful in differentiating cancer from benign prostatic enlargement.

There are three different patterns of flow changes noted in the case of a cancerous lesion: focal flow, increased flow around a distinct nodule, and asymmetrical flow on the cancerous side with an increase in the size and number of feeding vessels. Overall, the usage of conventional Doppler increases the specificity by approximately 5%–10% (42),[34] Conventional Doppler techniques are not specific and sensitive enough to replace the systematic biopsy protocol as of today.


  Conclusion Top


The incidence of prostate cancer is on the rise leading to significant morbidity and mortality worldwide, especially in the developed world. Today, TRUS-guided biopsy, under local anaesthesia and prophylactic antibiotics, is the most widely accepted method to diagnose prostate cancer. The sensitivity and specificity of grayscale TRUS for detecting prostate cancer remains low. Cancerous lesions most commonly appear as a hypoechoic focus in the peripheral zone; however, its characteristics can vary with substantial overlap with benign lesions. The number of cores obtained on systematic biopsies has increased over the years, with 10–12 cores currently recognized as the minimum standard.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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